Background: The preferred surgical approach for esophageal cancer is a minimally invasive transthoracic esophagectomy with a two-field lymph node dissection. The thoracoscopic phase may be performed either in prone- or in left lateral decubitus (LLD) position. Prone positioning has been associated with better pulmonary outcomes compared to LLD positioning; however, conversion to a classic thoracotomy is more difficult. The semiprone position has been proposed as an alternative approach. Methods: A retrospective review of a prospectively maintained database (2008–2014) was performed to compare postoperative complications, surgical radicality, and lymph node yield between patients who underwent three-stage minimally invasive transthoracic esophagectomy in either the prone or semiprone position. Comparative analyses were conducted before and after propensity score matching. Results: One hundred and twenty-one patients were included. In total, 82 patients underwent minimally invasive esophagectomy (MIE) in semiprone position and 39 patients in prone position. After propensity score matching, both groups consisted of 39 patients. The operative time in the semiprone group was longer (368 vs. 225 min, P < 0.001) and in this group the lymph node yield was significantly higher (16 (range 6–80) vs. 13 (range 3–33), P = 0.019). There were no statistically significant differences regarding radical resections, postoperative complications, and hospital stay. Conclusion: The use of semiprone positioning in MIE is safe, feasible, and at least comparable to MIE in prone position in terms of oncological clearance and postoperative complications
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